Among human rickettsial diseases caused by micro-organisms of the genus Rickettsia (Order Rickettsiales; Family Rickettsiaceae), transmitted to human hosts through arthropod vectors, Mediterranean Spotted Fever, or Boutonneuse Fever, and Rocky Mountain Spotted Fever are considered to be important infectious diseases due to continued prevalence in the developed world, and potentially fatal outcome in severe cases. Proliferation of rickettsiae, at the site of the tick bite, results in focal epidermal and dermal necrosis (tache noire). Rickettsiae then spread via lymphatic vessels to the regional lymph nodes, and, via the bloodstream, to skin, brain, lungs, heart, liver, spleen and kidneys. The pathogen invades and proliferates in the endothelial cells of small vessels, target cells of rickettsial infection, destroying them, and spreading the infection to the endothelia of the vascular tree. The damage of the endothelium, and the subsequent endothelia dysfunction, is followed by the activation of acute phase responses, with alteration in the coagulation and in the cytokine network, together with a transient immune dysregulation, characterized by the reduction in peripheral CD4+ T lymphocytes
